Comparison of Chemotherapy Before and After Surgery Versus After Surgery Alone for the Treatment of Gallbladder Cancer

Stage III Gallbladder Cancer AJCC v8 Clinical Trial

Official title:

Optimal Perioperative Therapy for Incidental Gallbladder Cancer (OPT-IN): A Randomized Phase II/III Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04559139
• Other study ID #: EA2197
• Secondary ID: NCI-2020-05162EA
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: February 24, 2021
• Est. completion date: June 30, 2029

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II/III trial compares the effect of adding chemotherapy before and after surgery versus after surgery alone (usual treatment) in treating patients with stage II-III gallbladder cancer. Chemotherapy drugs, such as gemcitabine and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before surgery may make the tumor smaller; therefore, may reduce the extent of surgery. Additionally, it may make it easier for the surgeon to distinguish between normal and cancerous tissue. Giving chemotherapy after surgery may kill any remaining tumor cells. This study will determine whether giving chemotherapy before surgery increases the length of time before the cancer may return and whether it will increase a patient's life span compared to the usual approach.

Description:

PRIMARY OBJECTIVE:

I. To determine the difference in overall survival (OS) for patients given neoadjuvant gemcitabine hydrochloride (gemcitabine) and cisplatin prior to re-resection followed by adjuvant gemcitabine and cisplatin compared to patients who receive only adjuvant gemcitabine and cisplatin after re-resection for incidental gallbladder cancer (IGBC).

SECONDARY OBJECTIVES:

I. To compare the incidence of residual disease at the time of re-resection between patients with IGBC who receive perioperative chemotherapy prior to re-resection and those who receive only adjuvant chemotherapy after re-resection.

II. To assess the clinical effect of preoperative chemotherapy compared to upfront re-resection on resectability among 3 cohorts: all enrolled patients, all patients who undergo staging laparoscopy, and all patients who undergo laparotomy.

III. To determine the difference in progression-free survival (PFS) for patients with IGBC who receive perioperative chemotherapy prior to and after re-resection compared to patients who receive only adjuvant chemotherapy after re-resection.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Within 4 weeks of randomization, patients undergo surgery to remove part of the liver, the lymph nodes around the liver, and possibly the bile ducts. Patients then receive gemcitabine intravenously (IV) over 30 minutes and cisplatin IV over 30 minutes-24 hours on days 1 and 8. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive gemcitabine IV over 30 minutes and cisplatin over 30 minutes-24 hours on days 1 and 8. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Approximately 4-8 weeks after completion of chemotherapy, patients whose disease has not spread to other places in the body (metastasized) undergo surgery as in Arm I. Patients with successful surgery then resume treatment with gemcitabine IV and cisplatin IV on days 1 and 8. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for 1 year after surgery or until disease recurrence, whichever comes first, for up to 5 years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 186
• Est. completion date: June 30, 2029
• Est. primary completion date: June 30, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

• Patient must have histologically-confirmed T2 or T3 gallbladder cancer discovered incidentally at the time of or following routine cholecystectomy for presumed benign disease

• NOTE: Patients with histologically-confirmed Tis, T1a, T1b, or T4 tumors are not eligible

• Patient must have undergone initial cholecystectomy within 12 weeks prior to randomization

• Patient must have the ability to understand and the willingness to sign a written informed consent document

• Leukocytes >= 3,000/mcL (obtained =< 28 days prior to randomization)

• Absolute neutrophil count >= 1,500/mcL (obtained =< 28 days prior to randomization)

• Platelets >= 100,000/mcL (obtained =< 28 days prior to randomization)

• Total bilirubin =< institutional upper limit of normal (ULN) except in patients with Gilbert's syndrome. Patients with Gilbert's syndrome are eligible if direct bilirubin < 1.5 x ULN of the direct bilirubin (obtained =< 28 days prior to randomization)

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained =< 28 days prior to randomization)

• Serum creatinine =< institutional ULN OR creatinine clearance >= 50 mL/min/1.73 m^2 (Based on Cockcroft Gault estimation) (obtained =< 28 days prior to randomization)

• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial

• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated

• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification. To be eligible for this trial, patients should be class 2B or better

Exclusion Criteria:

• Patient must not have any evidence of metastatic disease or inoperable loco-regional disease based on high-quality, preoperative, cross-sectional imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) of the chest, abdomen, and pelvis (C/A/P) obtained within 6 weeks prior to randomization, defined as

• No radiographic evidence of distant disease (M1 disease)

• No radiographic evidence of tumor invasion into multiple extrahepatic organs (T4 disease)

• No radiographic evidence of distant lymph node involvement (celiac, para-aortic, para-caval lymph nodes)

• No evidence of new-onset ascites

• Soft tissue thickening within or in direct communication with the gallbladder fossa, peri-portal lymph node involvement, involvement of one extrahepatic organ, and other disease within the confines of what constitutes 'localized resectable' disease are allowable

• Women must not be pregnant or breast feeding due to the potential harm to unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All females of child bearing potential must have a serum or urine pregnancy test to rule out pregnancy within 14 days prior to randomization. A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

• Women of childbearing potential and sexually active males must not expect to conceive or father children by being strongly advised to use accepted and effective method(s) of contraception or to abstain from sexual intercourse for the duration of their participation in the study

Related Conditions & MeSH terms

• Gallbladder Neoplasms
• Stage II Gallbladder Cancer AJCC v8
• Stage IIA Gallbladder Cancer AJCC v8
• Stage IIB Gallbladder Cancer AJCC v8
• Stage III Gallbladder Cancer AJCC v8
• Stage IIIA Gallbladder Cancer AJCC v8
• Stage IIIB Gallbladder Cancer AJCC v8

Intervention

Drug:
• Cisplatin
Given IV
• Gemcitabine Hydrochloride
Given IV

Procedure:
• Lymphadenectomy
Undergo portal lymphadenectomy
• Partial Hepatectomy
Undergo partial hepatectomy

Locations

Country	Name	City	State
United States	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington
United States	Albany Medical Center	Albany	New York
United States	Lovelace Medical Center-Saint Joseph Square	Albuquerque	New Mexico
United States	Presbyterian Kaseman Hospital	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Saint Anthony's Health	Alton	Illinois
United States	Alaska Breast Care and Surgery LLC	Anchorage	Alaska
United States	Alaska Oncology and Hematology LLC	Anchorage	Alaska
United States	Alaska Women's Cancer Care	Anchorage	Alaska
United States	Anchorage Associates in Radiation Medicine	Anchorage	Alaska
United States	Anchorage Oncology Centre	Anchorage	Alaska
United States	Anchorage Radiation Therapy Center	Anchorage	Alaska
United States	Katmai Oncology Group	Anchorage	Alaska
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Mission Hope Medical Oncology - Arroyo Grande	Arroyo Grande	California
United States	Emory Saint Joseph's Hospital	Atlanta	Georgia
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	UM Sylvester Comprehensive Cancer Center at Aventura	Aventura	Florida
United States	Saint Louis Cancer and Breast Institute-Ballwin	Ballwin	Missouri
United States	Flaget Memorial Hospital	Bardstown	Kentucky
United States	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	Indu and Raj Soin Medical Center	Beavercreek	Ohio
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Saint Charles Health System	Bend	Oregon
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Elizabeth Boardman Hospital	Boardman	Ohio
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Central Care Cancer Center - Bolivar	Bolivar	Missouri
United States	Cox Cancer Center Branson	Branson	Missouri
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Harrison Medical Center	Bremerton	Washington
United States	United Hospital Center	Bridgeport	West Virginia
United States	University of Michigan - Brighton Center for Specialty Care	Brighton	Michigan
United States	Saint Joseph Regional Cancer Center	Bryan	Texas
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Memorial Hospital of Carbondale	Carbondale	Illinois
United States	Mercy Cancer Center ?? Carmichael	Carmichael	California
United States	Mercy San Juan Medical Center	Carmichael	California
United States	Saint Anthony Regional Hospital	Carroll	Iowa
United States	SIH Cancer Institute	Carterville	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio
United States	Miami Valley Hospital South	Centerville	Ohio
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	Saint Mary's Hospital	Centralia	Illinois
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Westside	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Baptist Memorial Hospital and Cancer Center-Collierville	Collierville	Tennessee
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	Saint Francis Cancer Center	Colorado Springs	Colorado
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Memorial Sloan Kettering Commack	Commack	New York
United States	Bay Area Hospital	Coos Bay	Oregon
United States	UM Sylvester Comprehensive Cancer Center at Coral Gables	Coral Gables	Florida
United States	Commonwealth Cancer Center-Corbin	Corbin	Kentucky
United States	Alegent Health Mercy Hospital	Council Bluffs	Iowa
United States	Greater Regional Medical Center	Creston	Iowa
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	Parkland Memorial Hospital	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Dayton Blood and Cancer Center	Dayton	Ohio
United States	Dayton Physician LLC-Miami Valley Hospital North	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	UM Sylvester Comprehensive Cancer Center at Deerfield Beach	Deerfield Beach	Florida
United States	Northwestern Medicine Cancer Center Kishwaukee	DeKalb	Illinois
United States	Porter Adventist Hospital	Denver	Colorado
United States	Broadlawns Medical Center	Des Moines	Iowa
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Illinois CancerCare-Dixon	Dixon	Illinois
United States	Mercy Medical Center	Durango	Colorado
United States	Southwest Oncology PC	Durango	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Swedish Cancer Institute-Edmonds	Edmonds	Washington
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Mercy Cancer Center - Elk Grove	Elk Grove	California
United States	Elmhurst Memorial Hospital	Elmhurst	Illinois
United States	Saint Elizabeth Hospital	Enumclaw	Washington
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Inova Schar Cancer Institute	Fairfax	Virginia
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Medical Center Fargo	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Sanford South University Medical Center	Fargo	North Dakota
United States	Southpointe-Sanford Medical Center Fargo	Fargo	North Dakota
United States	Parkland Health Center - Farmington	Farmington	Missouri
United States	Saint Francis Hospital	Federal Way	Washington
United States	Armes Family Cancer Center	Findlay	Ohio
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Orion Cancer Care	Findlay	Ohio
United States	Trinity Regional Medical Center	Fort Dodge	Iowa
United States	Regional Cancer Center-Lee Memorial Health System	Fort Myers	Florida
United States	Mercy Hospital Fort Smith	Fort Smith	Arkansas
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Dayton Physicians LLC-Atrium	Franklin	Ohio
United States	Vanderbilt-Ingram Cancer Center at Franklin	Franklin	Tennessee
United States	Vanderbilt-Ingram Cancer Center Cool Springs	Franklin	Tennessee
United States	Queens Medical Associates PC	Fresh Meadows	New York
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	Central Care Cancer Center - Garden City	Garden City	Kansas
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Trinity Health Grand Rapids Hospital	Grand Rapids	Michigan
United States	Central Care Cancer Center - Great Bend	Great Bend	Kansas
United States	Dayton Physicians LLC-Wayne	Greenville	Ohio
United States	Wayne Hospital	Greenville	Ohio
United States	Baptist Cancer Center-Grenada	Grenada	Mississippi
United States	Legacy Mount Hood Medical Center	Gresham	Oregon
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	CHI Saint Vincent Cancer Center Hot Springs	Hot Springs	Arkansas
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	Capital Region Southwest Campus	Jefferson City	Missouri
United States	NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro	Jonesboro	Arkansas
United States	Freeman Health System	Joplin	Missouri
United States	Mercy Hospital Joplin	Joplin	Missouri
United States	Ascension Borgess Cancer Center	Kalamazoo	Michigan
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Greater Dayton Cancer Center	Kettering	Ohio
United States	Kettering Medical Center	Kettering	Ohio
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	University of Tennessee - Knoxville	Knoxville	Tennessee
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Providence Regional Cancer System-Lacey	Lacey	Washington
United States	Northwell Health/Center for Advanced Medicine	Lake Success	New York
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Saint Clare Hospital	Lakewood	Washington
United States	Saint Joseph Hospital	Lexington	Kentucky
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Saint Joseph London	London	Kentucky
United States	Longmont United Hospital	Longmont	Colorado
United States	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado
United States	PeaceHealth Saint John Medical Center	Longview	Washington
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Jewish Hospital	Louisville	Kentucky
United States	Saints Mary and Elizabeth Hospital	Louisville	Kentucky
United States	The James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky
United States	UofL Health Medical Center Northeast	Louisville	Kentucky
United States	Lowell General Hospital	Lowell	Massachusetts
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	North Shore University Hospital	Manhasset	New York
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	WVUH-Berkely Medical Center	Martinsburg	West Virginia
United States	Baptist Memorial Hospital and Cancer Center-Memphis	Memphis	Tennessee
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	UM Sylvester Comprehensive Cancer Center at Kendall	Miami	Florida
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Memorial Sloan Kettering Monmouth	Middletown	New Jersey
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Memorial Sloan Kettering Bergen	Montvale	New Jersey
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	Saint Joseph Mount Sterling	Mount Sterling	Kentucky
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Trinity Health Muskegon Hospital	Muskegon	Michigan
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Edward Hospital/Cancer Center	Naperville	Illinois
United States	Vanderbilt Breast Center at One Hundred Oaks	Nashville	Tennessee
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	Baptist Memorial Hospital and Cancer Center-Union County	New Albany	Mississippi
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	UC Comprehensive Cancer Center at Silver Cross	New Lenox	Illinois
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Lakeland Hospital Niles	Niles	Michigan
United States	Cancer and Hematology Centers of Western Michigan - Norton Shores	Norton Shores	Michigan
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Alegent Health Lakeside Hospital	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	Providence Willamette Falls Medical Center	Oregon City	Oregon
United States	University of Chicago Medicine-Orland Park	Orland Park	Illinois
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Baptist Memorial Hospital and Cancer Center-Oxford	Oxford	Mississippi
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	Midlands Community Hospital	Papillion	Nebraska
United States	Parker Adventist Hospital	Parker	Colorado
United States	Camden Clark Medical Center	Parkersburg	West Virginia
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Cancer Center at Saint Joseph's	Phoenix	Arizona
United States	Edward Hospital/Cancer Center?Plainfield	Plainfield	Illinois
United States	UM Sylvester Comprehensive Cancer Center at Plantation	Plantation	Florida
United States	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon
United States	Oregon Health and Science University	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Saint Charles Health System-Redmond	Redmond	Oregon
United States	Spectrum Health Reed City Hospital	Reed City	Michigan
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	UT Southwestern Clinical Center at Richardson/Plano	Richardson	Texas
United States	Reid Health	Richmond	Indiana
United States	Presbyterian Rust Medical Center/Jorgensen Cancer Center	Rio Rancho	New Mexico
United States	Highland Hospital	Rochester	New York
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Mercy Cancer Center - Rocklin	Rocklin	California
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Mercy Cancer Center - Sacramento	Sacramento	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan
United States	Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Mercy Hospital South	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Siteman Cancer Center at Christian Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center-South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Pacific Central Coast Health Center-San Luis Obispo	San Luis Obispo	California
United States	Mission Hope Medical Oncology - Santa Maria	Santa Maria	California
United States	Low Country Cancer Care	Savannah	Georgia
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	Summit Cancer Care-Memorial	Savannah	Georgia
United States	Pacific Gynecology Specialists	Seattle	Washington
United States	Swedish Medical Center-Ballard Campus	Seattle	Washington
United States	Swedish Medical Center-Cherry Hill	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	PeaceHealth United General Medical Center	Sedro-Woolley	Washington
United States	Providence Regional Cancer System-Shelton	Shelton	Washington
United States	Jewish Hospital Medical Center South	Shepherdsville	Kentucky
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Baptist Memorial Hospital and Cancer Center-Desoto	Southhaven	Mississippi
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Springfield Regional Cancer Center	Springfield	Ohio
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri
United States	Franciscan Research Center-Northwest Medical Plaza	Tacoma	Washington
United States	Northwest Medical Specialties PLLC	Tacoma	Washington
United States	Sanford Thief River Falls Medical Center	Thief River Falls	Minnesota
United States	Torrance Memorial Medical Center	Torrance	California
United States	Torrance Memorial Physician Network - Cancer Care	Torrance	California
United States	Munson Medical Center	Traverse City	Michigan
United States	Dayton Physicians LLC - Troy	Troy	Ohio
United States	Upper Valley Medical Center	Troy	Ohio
United States	Legacy Meridian Park Hospital	Tualatin	Oregon
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	Memorial Sloan Kettering Nassau	Uniondale	New York
United States	Legacy Cancer Institute Medical Oncology and Day Treatment	Vancouver	Washington
United States	Legacy Salmon Creek Hospital	Vancouver	Washington
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington
United States	Saint Joseph Warren Hospital	Warren	Ohio
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	Illinois CancerCare - Washington	Washington	Illinois
United States	Mercy Hospital Washington	Washington	Missouri
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Methodist West Hospital	West Des Moines	Iowa
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Woodland Memorial Hospital	Woodland	California
United States	Sanford Cancer Center Worthington	Worthington	Minnesota
United States	Metro Health Hospital	Wyoming	Michigan
United States	Providence Regional Cancer System-Yelm	Yelm	Washington
United States	Saint Elizabeth Youngstown Hospital	Youngstown	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
ECOG-ACRIN Cancer Research Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in overall survival	Will compare patients with incidental gallbladder cancer (IGBC) who receive perioperative chemotherapy prior to and after re-resection with patients who receive only adjuvant chemotherapy after re-resection. Will be evaluated by stratified log rank test, and Kaplan-Meier analyses will be used to calculate and display the overall survival distributions among all randomized patients on the two study arms (intention-to-treat analysis).	Time from randomization to death or last follow-up, assessed up to 5 years
Secondary	Incidence of residual disease	Will compare the incidence of residual disease which is defined as the presence of either microscopic or gross malignancy based on pathologic analysis of the re-resection specimen at the time of re-resection between patients with IGBC who receive perioperative chemotherapy prior to re-resection and those who receive only adjuvant chemotherapy after re-resection. Residual disease is defined as the presence of either microscopic or gross malignancy based on pathologic analysis of the re-resection specimen.	At the time of re-resection, through study completion, an average of 5 years.
Secondary	Overall resectability rate	Will be defined as the proportion of patients who successfully undergo a re-resection versus all enrolled patients. Descriptive statistics will be performed to calculate the number, proportion of patients, and 95% confidence intervals for the resectability and residual disease outcomes. Patients who do not undergo reoperation or re-resection, have incomplete resections (R2), or who have gross evidence of distant metastases and/or T4 disease will be considered as unresectable for resectability analyses.	Up to 5 years
Secondary	Resectability rate	Will be defined as the proportion of patients who successfully undergo a re-resection versus all patients who undergo screening laparoscopy. Descriptive statistics will be performed to calculate the number, proportion of patients, and 95% confidence intervals for the resectability and residual disease outcomes. Patients who do not undergo reoperation or re-resection, have incomplete resections (R2), or who have gross evidence of distant metastases and/or T4 disease will be considered as unresectable for resectability analyses.	At the time of diagnostic laparoscopy, through study completion, an average of 5 years.
Secondary	Resectability rate	Will be defined as the proportion of patients who successfully undergo a re-resection versus all patients who undergo laparotomy. Descriptive statistics will be performed to calculate the number, proportion of patients, and 95% confidence intervals for the resectability and residual disease outcomes. Patients who do not undergo reoperation or re-resection, have incomplete resections (R2), or who have gross evidence of distant metastases and/or T4 disease will be considered as unresectable for resectability analyses.	At the time of laparotomy, through study completion, an average of 5 years.
Secondary	Difference in progression-free survival	Will compare patients given neoadjuvant gemcitabine and cisplatin with patients who receive only adjuvant gemcitabine and cisplatin after re-resection for IGCB. A stratified log rank test, along with Kaplan-Meier curves, will be used to analyze progression-free survival among all evaluable patients.	From randomization to first observed radiographic disease progression that is inoperable (either locoregional or distant metastatic), or death from any cause, assessed up to 5 years